Cdk4 is a target of c-myc

Details Cdk4 is a target of c-myc Cdk4 is a target of c-myc

C - Chemistry, Metallurgy

12

N

C12N 15/54 (2006.01) C07K 14/82 (2006.01) C12N 9/12 (2006.01) C12Q 1/68 (2006.01)

Patent

CA 2398580

The prototypic oncogene c-MYC encodes a transcription factor, which can drive proliferation by promoting cell cycle re-entry. However, the mechanisms through which c-MYC achieves these effects have been unclear. Using serial analysis of gene expression (SAGE), we have identified the cyclin dependent kinase 4 (CDK4) gene as a transcriptional target of c-MYC. c-MYC induced a rapid increase in CDK4 mRNA levels through four highly conserved c-Myc binding sites (MBS) within the CDK4 promoter. Cell cycle progression is delayed in c- MYC-deficient RAT1 cells, and this delay was associated with a defect in CDK4 induction. Ectopic expression of CDK4 in these cells partially alleviated the growth defect. Thus CDK4 provides a direct link between the oncogenic effects of c-MYC and cell cycle regulation.

L'invention concerne l'oncogène prototypique ic-MYC qui code un facteur de transcription pouvant susciter une prolifération par la promotion du renouvellement du cycle cellulaire. Le mécanisme par lequel c-MYC a ces effets n'était toutefois pas clair jusqu'à présent. Sur la base d'analyses sérielles de l'expression génétique (SAGE), nous avons identifié le gène kinase 4 (CDK4) dépendante des cyclines comme cible de transcription de c-MYC. c-MYC provoque une augmentation rapide dans les niveaux CDK4 mRNA à travers quatre sites c-Myc (MBS) à fort pouvoir de conservation à l'intérieur du promoteur CDK4. La progression du cycle cellulaire est retardée dans les cellules RAT1 déficientes en c-MYC, et ce retard est associé à une anomalie d'induction CDK4. L'expression ectopique de CDK4 dans ces cellules atténue partiellement le défaut de croissance. Ainsi, CDK4 présente une liaison directe entre les effets oncogènes de c-MYC et la régulation du cycle cellulaire.

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